Nearly a quarter of a century ago the treatment of breast cancer was changed after the inception of a drug called Herceptin. It targeted breast cancer connected to a gene, HER2. Fast forward a quarter-century and another breakthrough has been made. Daiichi Sankyo and AstraZeneca’s Enhertu clinical trial revealed that it reduced the risk of cancer progression by 50% compared to chemotherapy, also reducing the death risk by 36%.
However, there are certain limitations. Enhertu is related to some lung scarring which may require monitoring to identify and manage. It’s unknown how long the benefits of Enhertu might stay due to the short length of follow-ups. The effectiveness of the drug in triple-negative patients is also unknown because the level of HER2 required is not known.
Despite these hindrances, the drug is set to change the treatment of breast cancer according to experts. William Jacot, a medical oncologist at Montpellier Cancer Institute said that the results of the trial were unexpectedly very impressive. Cleveland Clinic’s Taussig Cancer Institute’s director of breast medical oncology, Halle Moore said that the survival numbers were very meaningful.
HER2 presence has always been considered in terms of either black or white, meaning a patient could only be considered as negative or positive. However, nearly half of the metastatic breast cancer patients are someplace in the middle of the two. Such patients have a low level of HER2, which is still detectable. Enhertu could be the first drug for such patients since chemotherapy and Herceptin are not beneficial for such patients. Enhertu could also aid in categorizing breast cancer by the amount of protein in it.
HER2 dates back to the 1980s, showing large amounts of the protein in some tumors. A lot of research took place, after which Herceptin was discovered, gaining a lot of ground in a short period of time. There was high demand for fast access. Moore described Herceptin as a game-changer.
HER2 tumors may evolve and start resisting drugs, which naturally calls for better treatment options. Daiichi developed Enhertu, which connects an antibody to a toxic payload chemically. The drug showed incredible potential, which was recognized by AstraZeneca and it ended up paying $7B for partial rights three years ago.
A few months after the deal, Enhertu’s breast cancer treatment enjoyed a lot of success in late-stage breast cancer trials, gaining clearance for third-line use. This year it also gained clearance for second-line use. Predicted annual sales of the drug in 2026 are north of $4B. In 2021, Enhertu closed at outside Japan sales of $426M.
Anticipating Enhertu becoming the first treatment for low HER2 disease, investors are closely following the details of the study at ASCO. Successful trial results for slowing down cancer progression and survival are indicators that Enhertu by AstraZeneca reduces breast cancer risk.
Nancy Lin, a medical oncologist at Dana-Farber Cancer Institute, told patients Enhertu feels like chemotherapy, considering they had similar side effects. However, 12% of the patients treated with Enhertu faced lung scarring, which turned out to be fatal for 3 of them. Lin said that doctors are improving in the identification of the side effects but they should still be cautious when prescribing the drug.
The way forward for the medical professionals is to create a new third category that represents patients that are ‘HER2 low’, the other two categories being ‘positive’ and ‘negative’. This will make people realize that HER2 low is something other than being completely negative or completely positive.